Article
Immunology
Seon-Young Park, HyeJin Yang, Minsook Ye, Xiao Liu, Insop Shim, Young-Tae Chang, Hyunsu Bae
Summary: This study found that adoptive transfer of Tregs can improve neurodegeneration in TMT-intoxicated mice by promoting neurogenesis and modulating microglial activation and polarization.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Immunology
Xiyuan Bai, Deepshikha Verma, Cindy Garcia, Ariel Musheyev, Kevin Kim, Lorelenn Fornis, David E. Griffith, Li Li, Nicholas Whittel, Jacob Gadwa, Tamara Ohanjanyan, Matthew J. Eggleston, Manuel Galvan, Brian M. Freed, Diane Ordway, Edward D. Chan
Summary: Cigarette smoke exposure can impair the immune response against Mycobacterium tuberculosis (MTB) infection. In this study, it was found that cigarette smoke-exposed T regulatory cells (Tregs) can exacerbate MTB infection by impairing macrophage function and promoting immunosuppression. This was demonstrated through co-culture experiments and mouse models. These findings suggest that cigarette smoke not only directly affects immune cells, but also indirectly promotes TB infection through the modulation of Tregs.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Immunology
Linda M. Lee, Hong Zhang, Karim Lee, Horace Liang, Alexander Merleev, Flavio Vincenti, Emanual Maverakis, Angus W. Thomson, Qizhi Tang
Summary: In this study comparing arTregs expanded ex vivo using different types of antigen-presenting cells, it was found that sDCs stimulated Tregs to expand in much larger numbers. Additionally, sDC-generated arTregs expressed higher levels of CD80, CD86, and T cell-attracting chemokines, indicating their superior expansion-inducing capacity.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Neurosciences
Alireza Faridar, Matthew Vasquez, Aaron D. Thome, Zheng Yin, Hui Xuan, Jing Hong Wang, Shixiang Wen, Xuping Li, Jason R. Thonhoff, Weihua Zhao, Hong Zhao, David R. Beers, Stephen T. C. Wong, Joseph C. Masdeu, Stanley H. Appel
Summary: This study demonstrates that ex vivo expanded Tregs can suppress neuroinflammation and alleviate amyloid pathology in a preclinical mouse model of Alzheimer's disease. These findings provide potential therapeutic strategies for Treg cell therapy in AD.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Surgery
Katsuyoshi Shimozawa, Laura Contreras-Ruiz, Sofia Sousa, Ruan Zhang, Urvashi Bhatia, Kerry C. Crisalli, Lisa L. Brennan, Laurence A. Turka, James F. Markmann, Eva C. Guinan
Summary: The study compared the suitability of blood cells from pre- and post-transplant patients with healthy controls for Treg manufacturing, finding that Treg expansion capacity was preserved despite certain limitations. Leukapheresis post-transplant and the use of splenocytes as substitutes for PBMCs were developed to improve Treg yield. The research also demonstrated how characterizing cellular input populations can inform clinical trial design and Treg manufacturing requirements.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Chemistry, Multidisciplinary
Varvara G. Blinova, Natalia S. Novachly, Sofya N. Gippius, Abdullah Hilal, Yulia A. Gladilina, Daria D. Eliseeva, Dmitry D. Zhdanov
Summary: The study tracked the differentiation and maturation of Tregs CD4(+)CD25(+)FoxP3(+)CD127(low) cells over 7 days of cultivation under ex vivo conditions, showing that expanded eTregs have a Treg-specific phenotype and suppressive activity. As expansion progressed, upregulation of the FoxP3 gene was observed and associated with gradual demethylation in the T cell-specific demethylation region.
APPLIED SCIENCES-BASEL
(2021)
Article
Immunology
Joanna Balcerek, Brian R. Shy, Amy L. Putnam, Lisa M. Masiello, Angela Lares, Florinna Dekovic, Luis Acevedo, Michael R. Lee, Vinh Nguyen, Weihong Liu, Sreenivasan Paruthiyil, Jingying Xu, Ashley S. Leinbach, Jeffrey A. Bluestone, Qizhi Tang, Jonathan H. Esensten
Summary: The manufacturing outcomes of PolyTreg products were consistent across different clinical trials and production dates, with cell fold expansion primarily correlated to the initial cell number. Parameters such as manufacturing date, patient sex, and age did not significantly affect Treg cell expansion during product manufacturing.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Aaron D. Thome, Jason R. Thonhoff, Weihua Zhao, Alireza Faridar, Jinghong Wang, David R. Beers, Stanley H. Appel
Summary: This study demonstrates the therapeutic potential of ex vivo expanded regulatory T cell-derived extracellular vesicles (EVs) in suppressing pro-inflammatory responses in vitro and in mouse models. These EVs reduced pro-inflammatory transcripts, increased anti-inflammatory transcripts, and modulated inflammation in the diseased spinal cord, suggesting their potential for clinical use in human diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Chemistry, Multidisciplinary
Bohwa Han, Yeonju Song, Jeehun Park, Junsang Doh
Summary: This review discusses the use of nanomaterials to address the limitations of CAR-T cell therapy, including methods to improve expansion, gene delivery, and enhance antitumor functions. Understanding the biological principles behind various nanomaterials is crucial for their application in ex vivo engineering of T/NK cells.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Immunology
P. Alonso-Guallart, N. Llore, E. Lopes, S-B Kofman, S-H Ho, J. Stern, G. Pierre, K. Bruestle, Q. Tang, M. Sykes, A. Griesemer
Summary: A novel approach for expanding highly suppressive cynomolgus macaque polyspecific T-regs was developed, utilizing a combination of CD40L-engineered B cells with the potential to be translated to clinical studies. This method represents the first report to create polyspecific T-regs suitable for use in deceased-donor transplants.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2021)
Article
Neurosciences
Aaron D. Thome, Farah Atassi, Jinghong Wang, Alireza Faridar, Weihua Zhao, Jason R. Thonhoff, David R. Beers, Eugene C. Lai, Stanley H. Appel
Summary: In this study, a shift towards a pro-inflammatory peripheral immune response in patients with Parkinson's disease (PD) was identified, with the loss of suppressive functions of regulatory T cells (Tregs) being a significant contributing factor. Ex vivo expansion of Tregs restored and enhanced their suppressive functions, suggesting a potential cell therapeutic approach for patients with PD.
NPJ PARKINSONS DISEASE
(2021)
Article
Oncology
Shivan Sivakumar, Enas Abu-Shah, David J. Ahern, Edward H. Arbe-Barnes, Ashwin K. Jainarayanan, Nagina Mangal, Srikanth Reddy, Aniko Rendek, Alistair Easton, Elke Kurz, Michael Silva, Zahir Soonawalla, Lara R. Heij, Rachael Bashford-Rogers, Mark R. Middleton, Michael L. Dustin
Summary: The study found that T cells play a crucial role in pancreatic cancer, with regulatory T cells expressing high levels of immune inhibitory proteins, and CD8(+) T cells showing low PD-1 expression in an exhausted state. These findings provide a basis for the rational design of a new generation of therapeutic strategies for pancreatic cancer.
Article
Biochemical Research Methods
Feline E. Dijkgraaf, Mireille Toebes, Mark Hoogenboezem, Marjolijn Mertz, David W. Vredevoogd, Tiago R. Matos, Marcel B. M. Teunissen, Rosalie M. Luiten, Ton N. Schumacher
Summary: This ex vivo imaging approach allows for the study of immune cell behavior in human skin and can be applied to research on immune cell function in murine skin. The ability to track the spatiotemporal behavior of immune cells in skin, including their response to immune stimuli, provides a platform for investigating physiological immune cell behavior as well as immune cell behavior in skin diseases.
Article
Chemistry, Multidisciplinary
Ajay S. Thatte, Alex G. Hamilton, Benjamin E. Nachod, Alvin J. Mukalel, Margaret M. Billingsley, Rohan Palanki, Kelsey L. Swingle, Michael J. Mitchell
Summary: In this study, an ionizable lipid nanoparticle platform was developed to deliver Foxp3 mRNA to CD4(+) T cells, effectively engineering them into immunosuppressive cells. The results highlight the potential of this platform for engineering immunosuppressive T cells.
Article
Immunology
Etienne Masle-Farquhar, Yogesh Jeelall, Jacqueline White, Julia Bier, Elissa K. Deenick, Robert Brink, Keisuke Horikawa, Christopher Carl Goodnow
Summary: This study investigated the effects of CARD11 gene mutations on B and T lymphocytes in a disease associated with B cell expansion and T cell anergy, as well as in certain lymphomas. The results showed that the mutations increased the activation and proliferation of B and T lymphocytes following antigen receptor stimulation, and led to increased expression of checkpoint molecules on T cells. This study reveals CARD11 as an important positive regulator of T cells and highlights the cell-intrinsic effects of CARD11 mutations on T cell malignancies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
A. Magnani, M. Semeraro, F. Adam, C. Booth, L. Dupre, E. C. Morris, A. Gabrion, C. Roudaut, D. Borgel, A. Toubert, E. Clave, C. Abdo, G. Gorochov, R. Petermann, M. Guiot, M. Miyara, D. Moshous, E. Magrin, A. Denis, F. Suarez, C. Lagresle, A. M. Roche, J. Everett, A. Trinquand, M. Guisset, J. Xu Bayford, S. Hacein-Bey-Abina, A. Kauskot, R. Elfeky, C. Rivat, S. Abbas, H. B. Gaspar, E. Macintyre, C. Picard, F. D. Bushman, A. Galy, A. Fischer, E. Six, A. J. Thrasher, M. Cavazzana
Summary: This article presents the long-term follow-up results of gene therapy for patients with Wiskott-Aldrich syndrome, showing that lentiviral gene therapy provides sustained clinical benefits for these patients.
Review
Oncology
Emmanuel Donnadieu, Maik Luu, Miriam Alb, Brigitte Anliker, Silvia Arcangeli, Chiara Bonini, Biagio De Angelis, Rashmi Choudhary, David Espie, Anne Galy, Cam Holland, Zoltan Ivics, Chahrazade Kantari-Mimoun, Marie Jose Kersten, Ulrike Koehl, Chantal Kuhn, Bruno Laugel, Franco Locatelli, Ibtissam Marchiq, Janet Markman, Marta Angiola Moresco, Emma Morris, Helene Negre, Concetta Quintarelli, Michael Rade, Kristin Reiche, Matthias Renner, Eliana Ruggiero, Carmen Sanges, Hans Stauss, Maria Themeli, Jan Van den Brulle, Michael Hudecek, Monica Casucci
Summary: The article introduces current preclinical models used to test the safety of engineered T cells, emphasizes the limitations of existing models, and proposes potential measures for improvement.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Correction
Biochemistry & Molecular Biology
A. Magnani, M. Semeraro, F. Adam, C. Booth, L. Dupre, E. C. Morris, A. Gabrion, C. Roudaut, D. Borgel, A. Toubert, E. Clave, C. Abdo, G. Gorochov, R. Petermann, M. Guiot, M. Miyara, D. Moshous, E. Magrin, A. Denis, F. Suarez, C. Lagresle, A. M. Roche, J. Everett, A. Trinquand, M. Guisset, J. Xu Bayford, S. Hacein-Bey-Abina, A. Kauskot, R. Elfeky, C. Rivat, S. Abbas, H. B. Gaspar, E. Macintyre, C. Picard, F. D. Bushman, A. Galy, A. Fischer, E. Six, A. J. Thrasher, M. Cavazzana
Letter
Ophthalmology
SriniVas R. Sadda, Frank G. Holz, Giovanni Staurenghi, Alessandro Invernizzi, Jennifer Arnold, Ramin Tadayoni
Article
Rheumatology
Marie Binvignat, Gabriel Pires, Nicolas Tchitchek, Felicie Costantino, Alice Courties, David Klatzmann, Atul J. Butte, Bernard Combe, Maxime Dougados, Pascal Richette, Encarnita Mariotti-Ferrandiz, Francis Berenbaum, Jeremie Sellam
Summary: This study aimed to classify phenotypes in hand osteoarthritis (HOA) based on cardinal symptoms. Using the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) subscores and visual analog scale, a hierarchical agglomerative clustering analysis was performed on data from the Digital Cohort Design (DIGICOD). Five clusters were identified, indicating different levels of symptoms and associations with joint destruction and physical/psychological burden.
ARTHRITIS CARE & RESEARCH
(2023)
Article
Ophthalmology
R. Lejoyeux, S. Bonnin, D. Guindolet, B. Jacquiod, O. Erol, Y. Le Mer, H. Jeguirim, M. Mauget-Faysse, R. Tadayoni
Summary: This study aimed to determine the incidence of fovea plana in the French population with age-related cataract. By retrospectively screening consecutive patients who underwent cataract surgery in Rothschild Foundation Hospital between January and March 2021, with available preoperative analyzable OCT scans, it was found that fovea plana occurred in 9.8% of the 204 patients, with 20 of them having fovea plana. Although fovea plana is defined as an immature macula, it was not associated with poor visual acuity in the cohort.
EUROPEAN JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Cell Biology
Steicy Sobrino, Alessandra Magnani, Michaela Semeraro, Loredana Martignetti, Akira Cortal, Adeline Denis, Chloe Couzin, Capucine Picard, Jacinta Bustamante, Elisa Magrin, Laure Joseph, Cecile Roudaut, Aurelie Gabrion, Tayebeh Soheili, Corinne Cordier, Olivier Lortholary, Francois Lefrere, Frederic Rieux-Laucat, Jean-Laurent Casanova, Sylvain Bodard, Nathalie Boddaert, Adrian J. Thrasher, Fabien Touzot, Sophie Taque, Felipe Suarez, Ambroise Marcais, Agathe Guilloux, Chantal Lagresle-Peyrou, Anne Galy, Antonio Rausell, Stephane Blanche, Marina Cavazzana, Emmanuelle Six
Summary: X-linked chronic granulomatous disease (CGD) is a serious condition associated with defective phagocytosis, infections, and inflammatory complications. A clinical trial of lentivirus-based gene therapy was conducted on four patients, showing successful engraftment and clinical benefits in two patients, while the other two experienced loss of gene-corrected cells. Single-cell transcriptomic analysis revealed lower levels of hematopoietic stem cells (HSCs) in CGD patients, especially in those with poor engraftment. Aberrant HSC state and elevated interferon genes were identified as predictors of HSC engraftment failure.
CELL REPORTS MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Jean-Francois Llitjos, Cedric Auffray, Edwige Peju, Zakaria Ait Hamou, Christophe Rousseau, Aurelie Durand, Clemence Martin, Jean-Paul Mira, Pierre-Regis Burgel, Jean-Daniel Chiche, Maha Zohra Ladjemi, Bruno Lucas, Frederic Pene
Summary: Clinical observations suggest that the source of primary infection is a major determinant of further nosocomial pneumonia in critically ill patients with sepsis. This study used relevant double-hit animal models to investigate the impact of primary nonpulmonary or pulmonary sepsis on lung immunity. The results indicate that polymicrobial peritonitis and bacterial pneumonia confer susceptibility or resistance to secondary gram-negative pulmonary infection, respectively, through immune modulation and cross-talk between regulatory T cells and alveolar macrophages.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Rheumatology
Alexandre Le Joncour, Paul Regnier, Anna Maciejewski-Duval, Erwan Charles, Stephane Barete, Pierre Fouret, Michelle Rosenzwajg, David Klatzmann, Patrice Cacoub, David Saadoun
Summary: This study aimed to investigate the effect of phosphodiesterase 4 (PDE4) inhibition on neutrophil activation in Behcet's disease (BD). The results showed that surface markers, reactive oxygen species (ROS) production, and neutrophil extracellular traps (NETs) production were upregulated in BD patient neutrophils. Inhibition of PDE4 significantly reduced neutrophil surface activation markers, ROS production, NETosis, and genes and pathways related to innate immunity, intracellular signaling, and chemotaxis.
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Medicine, Research & Experimental
Guillaume Corre, Anne Galy
Summary: In cell and gene therapy, achieving the stable engraftment of an abundant and highly polyclonal population of gene-corrected cells is crucial for the successful and safe treatment of patients. Monitoring the relative abundance of individual vector insertion sites in patients' blood cells has become an important safety assessment due to the potential risks associated with integrative vectors. Different metrics, such as the Shannon index, are used to express clonal diversity, but comparing samples with different richness is challenging. A normalized version of the Shannon index, such as Pielou's index or Simpson's probability index, is proposed as a robust and useful tool for comparing sample evenness in gene therapy.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Article
Ophthalmology
Ramin Tadayoni, Glenn J. Jaffe, Frank G. Holz, Ursula Schmidt-Erfurth, Kanji Takahashi, Chui Ming Gemmy Cheung, Seenu M. Hariprasad, Kinfemichael Gedif, Rasmus Olsen, Catherine Best, Franklin Igwe, Peter K. Kaiser
Summary: The HAWK and HARRIER studies compared the efficacy and safety of brolucizumab and aflibercept in the treatment of neovascular age-related macular degeneration. This post hoc analysis aimed to evaluate the treatment outcomes and potential for interval extensions in eyes that still had disease activity 8 weeks after the loading phase. The results showed that brolucizumab-treated eyes had better fluid resolution and a higher potential for treatment interval extension compared to aflibercept-treated eyes during the first year of treatment.
OPHTHALMOLOGY AND THERAPY
(2023)
Article
Hematology
Roxane Labrosse, Julia I. Chu, Myriam A. Armant, John K. Everett, Danilo Pellin, Niharika Kareddy, Andrew L. Frelinger, Lauren A. Henderson, Amy E. O'Connell, Amlan Biswas, Jet Coenen-van der Spek, Alexandra Miggelbrink, Claudia Fiorini, Hriju Adhikari, Charles C. Berry, Vito Adrian Cantu, Johnson Fong, Jason Jaroslavsky, Derin F. Karadeniz, Quan-Zhen Li, Shantan Reddy, Aoife M. Roche, Chengsong Zhu, Jennifer S. Whangbo, Colleen Dansereau, Brenda Mackinnon, Emily Morris, Stephanie M. Koo, Wendy B. London, Safa Baris, Ahmet Ozen, Elif Karakoc-Aydiner, Jenny M. Despotovic, Lisa R. Forbes Satter, Akihiko Saitoh, Yuta Aizawa, Alejandra King, Mai Anh Thi Nguyen, Vy Do Uyen Vu, Scott B. Snapper, Anne Galy, Luigi D. Notarangelo, Frederic D. Bushman, David A. Williams, Sung-Yun Pai
Summary: Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder characterized by immunodeficiency, eczema, microthrombocytopenia, autoimmunity, and lymphoid malignancies. In a phase 1/2 clinical trial, gene therapy using a self-inactivating lentiviral vector was performed on 5 patients with severe WAS, resulting in positive outcomes and improvements in clinical and laboratory manifestations.
Review
Biotechnology & Applied Microbiology
Anne Galy, Ben Berkhout, Karine Breckpot, Chantal Pichon, Kristie Bloom, Hans-Peter Kiem, Michael D. Muhlebach, Joseph M. Mccune
Summary: The development of prophylactic or therapeutic medicines for infectious diseases is a top priority for global health organizations. Genetic technologies have opened up new possibilities in combating pathogens. Recent developments in the field of infectious diseases offer unprecedented hope and have far-reaching impacts.
HUMAN GENE THERAPY
(2023)
Correction
Oncology
Paraskevi Kogionou, Sotirios P. P. Fortis, Maria Goulielmaki, Nicolas Aubert, Panagiota Batsaki, Sotirios Ouzounis, Dionisis Cavouras, Gilles Marodon, Savvas Stokidis, Angelos D. D. Gritzapis, Constantin N. N. Baxevanis
Review
Biotechnology & Applied Microbiology
Valentina Buffa, Jose Roberto Alvarez Vargas, Anne Galy, Simone Spinozzi, Celine J. Rocca
Summary: Decades of experience in hematopoietic stem and progenitor cell transplantation have laid the foundation for current ex vivo gene therapies. With advancements in gene editing and patient conditioning, a new era of gene therapies using hematopoietic stem and progenitor cells is emerging. These therapies have the potential to treat various blood-related and non-blood-related inherited disorders.
FRONTIERS IN GENOME EDITING
(2023)
